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ISSN (Online): 1875-5607

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Review Article

The Situation of Small Molecules Targeting Key Proteins in combatting SARS-CoV-2: Synthesis, Metabolic Pathway, Mechanism of Action, and Potential Therapeutic Applications

Author(s): Farzaneh Sorouri, Zahra Emamgholipour, Maryam Keykhaee, Alireza Najafi, Loghman Firoozpour, Omid Sabzevari, Mohammad Sharifzadeh, Alireza Foroumadi and Mehdi Khoobi*

Volume 22, Issue 2, 2022

Published on: 08 March, 2021

Page: [273 - 311] Pages: 39

DOI: 10.2174/1389557521666210308144302

Price: $65

Abstract

Abstract: Due to the high mortality rate of the 2019 coronavirus disease (COVID-19) pandemic, there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, and mechanism of action of the existing drugs with potential therapeutic applications for COVID-19. Furthermore, we summarized the molecular docking stimulation of the medications related to key protein targets. These already established drugs could be further developed, and after their testing through clinical trials, they could be used as suitable therapeutic options for patients suffering from COVID-19.

Keywords: COVID-19, RdRp inhibitors, 3CLpro inhibitors, viral entry inhibitors, mechanism of action, metabolic pathway

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[1]
Tripp, R.A.; Tompkins, S.M. Roles of Host Gene and Non-coding RNA Expression in Virus Infection, 1st ed; Springer, 2018.
[http://dx.doi.org/10.1007/978-3-030-05369-7]
[2]
Corman, V.M.; Muth, D.; Niemeyer, D.; Drosten, C. Hosts and sources of endemic human coronaviruses. In: Advances in virus research; Margaret Kielian, T. C. M.; Marilyn J., Roossinck, Eds.; Elsevier, 2018; Vol. 100, pp. 163-188..
[http://dx.doi.org/10.1016/bs.aivir.2018.01.001]
[3]
Wan, Y.; Shang, J.; Graham, R.; Baric, R.S.; Li, F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J. Virol., 2020, 94(7), e00127-e00120.
[http://dx.doi.org/10.1128/JVI.00127-20] [PMID: 31996437]
[4]
Zhou, P.; Yang, X.-L.; Wang, X.-G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.-R.; Zhu, Y.; Li, B.; Huang, C.-L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. nature, 2020, 579(7798), 270-273.,
[5]
Liu, C.; Zhou, Q.; Li, Y.; Garner, L.V.; Watkins, S.P.; Carter, L.J.; Smoot, J.; Gregg, A.C.; Daniels, A.D.; Jervey, S. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases; ACS Publications, 2020.
[http://dx.doi.org/10.1021/acscentsci.0c00272]
[6]
Paraskevis, D.; Kostaki, E.G.; Magiorkinis, G.; Panayiotakopoulos, G.; Sourvinos, G.; Tsiodras, S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect. Genet. Evol., 2020, 79104212
[http://dx.doi.org/10.1016/j.meegid.2020.104212] [PMID: 32004758]
[7]
Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B-J.; Jiang, S. The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat. Rev. Microbiol., 2009, 7(3), 226-236.
[http://dx.doi.org/10.1038/nrmicro2090] [PMID: 19198616]
[8]
Du, L.; Yang, Y.; Zhou, Y.; Lu, L.; Li, F.; Jiang, S. MERS-CoV spike protein: a key target for antivirals. Expert Opin. Ther. Targets, 2017, 21(2), 131-143.
[http://dx.doi.org/10.1080/14728222.2017.1271415] [PMID: 27936982]
[9]
Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA, 2020, 323(18), 1824-1836.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[10]
Jiang, S.; Hillyer, C.; Du, L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol., 2020, 41(5), 355-359.
[http://dx.doi.org/10.1016/j.it.2020.03.007] [PMID: 32249063]
[11]
Wu, Z.; McGoogan, J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 2020.
[http://dx.doi.org/10.1001/jama.2020.2648]
[12]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N-H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[13]
Lauer, S.A.; Grantz, K.H.; Bi, Q.; Jones, F.K.; Zheng, Q.; Meredith, H.R.; Azman, A.S.; Reich, N.G.; Lessler, J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann. Intern. Med., 2020, 172(9), 577-582.
[http://dx.doi.org/10.7326/M20-0504] [PMID: 32150748]
[14]
Li, Q.; Guan, X.; Wu, P.; Wang, X.; Zhou, L.; Tong, Y.; Ren, R.; Leung, K.S.M.; Lau, E.H.Y.; Wong, J.Y.; Xing, X.; Xiang, N.; Wu, Y.; Li, C.; Chen, Q.; Li, D.; Liu, T.; Zhao, J.; Liu, M.; Tu, W.; Chen, C.; Jin, L.; Yang, R.; Wang, Q.; Zhou, S.; Wang, R.; Liu, H.; Luo, Y.; Liu, Y.; Shao, G.; Li, H.; Tao, Z.; Yang, Y.; Deng, Z.; Liu, B.; Ma, Z.; Zhang, Y.; Shi, G.; Lam, T.T.Y.; Wu, J.T.; Gao, G.F.; Cowling, B.J.; Yang, B.; Leung, G.M.; Feng, Z. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. N. Engl. J. Med., 2020, 382(13), 1199-1207.
[http://dx.doi.org/10.1056/NEJMoa2001316] [PMID: 31995857]
[15]
Pung, R.; Chiew, C.J.; Young, B.E.; Chin, S.; Chen, M.I.; Clapham, H.E.; Cook, A.R.; Maurer-Stroh, S.; Toh, M.P.H.S.; Poh, C.; Low, M.; Lum, J.; Koh, V.T.J.; Mak, T.M.; Cui, L.; Lin, R.V.T.P.; Heng, D.; Leo, Y.S.; Lye, D.C.; Lee, V.J.M. Singapore 2019 Novel Coronavirus Outbreak Research Team. Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures. Lancet, 2020, 395(10229), 1039-1046.
[http://dx.doi.org/10.1016/S0140-6736(20)30528-6] [PMID: 32192580]
[16]
Chan, J.F-W.; Yuan, S.; Kok, K-H.; To, K.K-W.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C.C-Y.; Poon, R.W-S.; Tsoi, H.W.; Lo, S.K.; Chan, K.H.; Poon, V.K.; Chan, W.M.; Ip, J.D.; Cai, J.P.; Cheng, V.C.; Chen, H.; Hui, C.K.; Yuen, K.Y. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet, 2020, 395(10223), 514-523.
[http://dx.doi.org/10.1016/S0140-6736(20)30154-9] [PMID: 31986261]
[17]
Phan, L.T.; Nguyen, T.V.; Luong, Q.C.; Nguyen, T.V.; Nguyen, H.T.; Le, H.Q.; Nguyen, T.T.; Cao, T.M.; Pham, Q.D. Importation and human-to-human transmission of a novel coronavirus in Vietnam. N. Engl. J. Med., 2020, 382(9), 872-874.
[http://dx.doi.org/10.1056/NEJMc2001272] [PMID: 31991079]
[18]
Liu, W.; Zhang, Q.; Chen, J.; Xiang, R.; Song, H.; Shu, S.; Chen, L.; Liang, L.; Zhou, J.; You, L.; Wu, P.; Zhang, B.; Lu, Y.; Xia, L.; Huang, L.; Yang, Y.; Liu, F.; Semple, M.G.; Cowling, B.J.; Lan, K.; Sun, Z.; Yu, H.; Liu, Y. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N. Engl. J. Med., 2020, 382(14), 1370-1371.
[http://dx.doi.org/10.1056/NEJMc2003717] [PMID: 32163697]
[19]
Liu, Y-C.; Liao, C-H.; Chang, C-F.; Chou, C-C.; Lin, Y-R. A locally transmitted case of SARS-CoV-2 infection in Taiwan. N. Engl. J. Med., 2020, 382(11), 1070-1072.
[http://dx.doi.org/10.1056/NEJMc2001573] [PMID: 32050059]
[20]
Kim, J.Y.; Ko, J-H.; Kim, Y.; Kim, Y-J.; Kim, J-M.; Chung, Y-S.; Kim, H.M.; Han, M-G.; Kim, S.Y.; Chin, B.S. Viral load kinetics of SARS-CoV-2 infection in first two patients in Korea. J. Korean Med. Sci., 2020, 35(7)e86
[http://dx.doi.org/10.3346/jkms.2020.35.e86] [PMID: 32080991]
[21]
Pan, Y.; Zhang, D.; Yang, P.; Poon, L.L.M.; Wang, Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect. Dis., 2020, 20(4), 411-412.
[http://dx.doi.org/10.1016/S1473-3099(20)30113-4] [PMID: 32105638]
[22]
Zou, L.; Ruan, F.; Huang, M.; Liang, L.; Huang, H.; Hong, Z.; Yu, J.; Kang, M.; Song, Y.; Xia, J.; Guo, Q.; Song, T.; He, J.; Yen, H.L.; Peiris, M.; Wu, J. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med., 2020, 382(12), 1177-1179.
[http://dx.doi.org/10.1056/NEJMc2001737] [PMID: 32074444]
[23]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. lancet, 2020, 395(10223), 497-506,
[24]
Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; Zhao, Y.; Li, Y.; Wang, X.; Peng, Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA, 2020, 323(11), 1061-1069.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[25]
Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; Xia, J.; Yu, T.; Zhang, X.; Zhang, L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(10223), 507-513.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[26]
Liu, Y.; Yang, Y.; Zhang, C.; Huang, F.; Wang, F.; Yuan, J.; Wang, Z.; Li, J.; Li, J.; Feng, C.; Zhang, Z.; Wang, L.; Peng, L.; Chen, L.; Qin, Y.; Zhao, D.; Tan, S.; Yin, L.; Xu, J.; Zhou, C.; Jiang, C.; Liu, L. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci. China Life Sci., 2020, 63(3), 364-374.
[http://dx.doi.org/10.1007/s11427-020-1643-8] [PMID: 32048163]
[27]
Zhang, B.; Zhou, X.; Qiu, Y.; Song, Y.; Feng, F.; Feng, J.; Song, Q.; Jia, Q.; Wang, J.; Liu, Z. Clinical characteristics of 82 cases of death from COVID-19. PLoS One, 2020, 15(7)e0235458
[http://dx.doi.org/10.1371/journal.pone.0235458] [PMID: 32645044]
[28]
Keicho, N.; Itoyama, S.; Kashiwase, K.; Phi, N.C.; Long, H.T.; Ha, L.D.; Ban, V.V.; Hoa, B.K.; Hang, N.T.; Hijikata, M.; Sakurada, S.; Satake, M.; Tokunaga, K.; Sasazuki, T.; Quy, T. Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population. Hum. Immunol., 2009, 70(7), 527-531.
[http://dx.doi.org/10.1016/j.humimm.2009.05.006] [PMID: 19445991]
[29]
Korber, B.; Fischer, W.M.; Gnanakaran, S.; Yoon, H.; Theiler, J.; Abfalterer, W.; Hengartner, N.; Giorgi, E.E.; Bhattacharya, T.; Foley, B.; Hastie, K.M.; Parker, M.D.; Partridge, D.G.; Evans, C.M.; Freeman, T.M.; de Silva, T.I.; McDanal, C.; Perez, L.G.; Tang, H.; Moon-Walker, A.; Whelan, S.P.; LaBranche, C.C.; Saphire, E.O.; Montefiori, D.C. Sheffield COVID-19 Genomics Group. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell, 2020, 182(4), 812-827.e19.
[http://dx.doi.org/10.1016/j.cell.2020.06.043] [PMID: 32697968]
[30]
Eastman, R.T.; Roth, J.S.; Brimacombe, K.R.; Simeonov, A.; Shen, M.; Patnaik, S.; Hall, M.D. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent. Sci., 2020, 6(6), 1009.
[http://dx.doi.org/10.1021/acscentsci.0c00747] [PMID: 32607448]
[31]
Sheahan, T.P.; Sims, A.C.; Graham, R.L.; Menachery, V.D.; Gralinski, L.E.; Case, J.B.; Leist, S.R.; Pyrc, K.; Feng, J.Y.; Trantcheva, I.; Bannister, R.; Park, Y.; Babusis, D.; Clarke, M.O.; Mackman, R.L.; Spahn, J.E.; Palmiotti, C.A.; Siegel, D.; Ray, A.S.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med., 2017, 9(396)eaal3653
[http://dx.doi.org/10.1126/scitranslmed.aal3653] [PMID: 28659436]
[32]
Furuta, Y.; Komeno, T.; Nakamura, T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2017, 93(7), 449-463.
[http://dx.doi.org/10.2183/pjab.93.027] [PMID: 28769016]
[33]
Luo, T.; Na, Y.; Tan, L. Ribavirin was beneficial for patients with SARS and MERS: uncertain if it is effective for patients with COVID-19. China Pharm., 2020, 29(5), 34-39.
[34]
Sidwell, R.W.; Huffman, J.H.; GP Khare, L. Broad-spectrum antiviral activity of virazole: 1-f8-D-ribofuranosyl-1, 2, 4-triazole-3-carboxamide. Science, 1972, 177(4050), 705-706.
[http://dx.doi.org/10.1126/science.177.4050.705] [PMID: 4340949]
[35]
Shaikh, V. S.; Shaikh, Y.; Ahmed, K. Lopinavir as a potential inhibitor for sars-cov-2 target protein: A Molecular Docking Study. Available at SSRN 3596820, 2020.
[36]
Gupta, S.; Senapati, S. Mechanism of inhibition of drug-resistant HIV-1 protease clinical isolates by TMC310911: A molecular dynamics study. J. Mol. Struct., 2019, 1198126893
[http://dx.doi.org/10.1016/j.molstruc.2019.126893]
[37]
Stellbrink, H-J.; Arastéh, K.; Schürmann, D.; Stephan, C.; Dierynck, I.; Smyej, I.; Hoetelmans, R.M.; Truyers, C.; Meyvisch, P.; Jacquemyn, B.; Mariën, K.; Simmen, K.; Verloes, R. Antiviral activity, pharmacokinetics, and safety of the HIV-1 protease inhibitor TMC310911, coadministered with ritonavir, in treatment-naive HIV-1-infected patients. J. Acquir. Immune Defic. Syndr., 2014, 65(3), 283-289.
[http://dx.doi.org/10.1097/QAI.0000000000000003] [PMID: 24121756]
[38]
Dong, L.; Hu, S.; Gao, J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov. Ther., 2020, 14(1), 58-60.
[http://dx.doi.org/10.5582/ddt.2020.01012] [PMID: 32147628]
[39]
Boriskin, Y.S.; Leneva, I.A.; Pécheur, E-I.; Polyak, S.J. Arbidol: a broad-spectrum antiviral compound that blocks viral fusion. Curr. Med. Chem., 2008, 15(10), 997-1005.
[http://dx.doi.org/10.2174/092986708784049658] [PMID: 18393857]
[40]
Vankadari, N. Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein. Int. J. Antimicrob. Agents, 2020, 56(2)105998
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105998] [PMID: 32360231]
[41]
Balakin, K.V.; Filosa, R.; Lavrenov, S.N.; Mkrtchyan, A.S.; Nawrozkij, M.B.; Novakov, I.A. Arbidol: a quarter-century after. Past, present and future of the original Russian antiviral. Russ. Chem. Rev., 2018, 87(6), 509.
[http://dx.doi.org/10.1070/RCR4791]
[42]
Shen, L.W.; Mao, H.J.; Wu, Y.L.; Tanaka, Y.; Zhang, W. TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections. Biochimie, 2017, 142, 1-10.
[http://dx.doi.org/10.1016/j.biochi.2017.07.016] [PMID: 28778717]
[43]
Yamamoto, M.; Kiso, M.; Sakai-Tagawa, Y.; Iwatsuki-Horimoto, K.; Imai, M.; Takeda, M.; Kinoshita, N.; Ohmagari, N.; Gohda, J.; Semba, K.; Matsuda, Z.; Kawaguchi, Y.; Kawaoka, Y.; Inoue, J.I. The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In vitro in a Cell-Type-Dependent Manner. Viruses, 2020, 12(6), 629.
[http://dx.doi.org/10.3390/v12060629] [PMID: 32532094]
[44]
Gao, Y.; Yan, L.; Huang, Y.; Liu, F.; Zhao, Y.; Cao, L.; Wang, T.; Sun, Q.; Ming, Z.; Zhang, L.; Ge, J.; Zheng, L.; Zhang, Y.; Wang, H.; Zhu, Y.; Zhu, C.; Hu, T.; Hua, T.; Zhang, B.; Yang, X.; Li, J.; Yang, H.; Liu, Z.; Xu, W.; Guddat, L.W.; Wang, Q.; Lou, Z.; Rao, Z. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 2020, 368(6492), 779-782.
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[45]
Warren, T.K.; Jordan, R.; Lo, M.K.; Ray, A.S.; Mackman, R.L.; Soloveva, V.; Siegel, D.; Perron, M.; Bannister, R.; Hui, H.C.; Larson, N.; Strickley, R.; Wells, J.; Stuthman, K.S.; Van Tongeren, S.A.; Garza, N.L.; Donnelly, G.; Shurtleff, A.C.; Retterer, C.J.; Gharaibeh, D.; Zamani, R.; Kenny, T.; Eaton, B.P.; Grimes, E.; Welch, L.S.; Gomba, L.; Wilhelmsen, C.L.; Nichols, D.K.; Nuss, J.E.; Nagle, E.R.; Kugelman, J.R.; Palacios, G.; Doerffler, E.; Neville, S.; Carra, E.; Clarke, M.O.; Zhang, L.; Lew, W.; Ross, B.; Wang, Q.; Chun, K.; Wolfe, L.; Babusis, D.; Park, Y.; Stray, K.M.; Trancheva, I.; Feng, J.Y.; Barauskas, O.; Xu, Y.; Wong, P.; Braun, M.R.; Flint, M.; McMullan, L.K.; Chen, S.S.; Fearns, R.; Swaminathan, S.; Mayers, D.L.; Spiropoulou, C.F.; Lee, W.A.; Nichol, S.T.; Cihlar, T.; Bavari, S. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 2016, 531(7594), 381-385.
[http://dx.doi.org/10.1038/nature17180] [PMID: 26934220]
[46]
Siegel, D.; Hui, H.C.; Doerffler, E.; Clarke, M.O.; Chun, K.; Zhang, L.; Neville, S.; Carra, E.; Lew, W.; Ross, B.; Wang, Q.; Wolfe, L.; Jordan, R.; Soloveva, V.; Knox, J.; Perry, J.; Perron, M.; Stray, K.M.; Barauskas, O.; Feng, J.Y.; Xu, Y.; Lee, G.; Rheingold, A.L.; Ray, A.S.; Bannister, R.; Strickley, R.; Swaminathan, S.; Lee, W.A.; Bavari, S.; Cihlar, T.; Lo, M.K.; Warren, T.K.; Mackman, R.L. Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses. J. Med. Chem., 2017, 60(5), 1648-1661.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01594] [PMID: 28124907]
[47]
Chun, B.K.; Clarke, M.O.N.H.; Doerffler, E.; Hui, H.C.; Jordan, R.; Mackman, R.L.; Parrish, J.P.; Ray, A.S.; Siegel, D. .Methods for treating Filoviridae virus infections. U.S. Patent 9,724,360, 2017 8August,
[48]
Vieira, T.; Stevens, A.; Chtchemelinine, A.; Gao, D.; Badalov, P.; Heumann, L. Development of a Large-Scale Cyanation Process Using Continuous Flow Chemistry en Route to the Synthesis of Remdesivir. Org. Process Res. Dev., 2020.
[http://dx.doi.org/10.1021/acs.oprd.0c00172]
[49]
Varga, A.; Lionne, C.; Roy, B. Intracellular metabolism of nucleoside/nucleotide analogues: a bottleneck to reach active drugs on HIV reverse transcriptase. Curr. Drug Metab., 2016, 17(3), 237-252.
[http://dx.doi.org/10.2174/1389200217666151210141903] [PMID: 26651972]
[50]
Slusarczyk, M.; Serpi, M.; Pertusati, F. Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. Antivir. Chem. Chemother., 2018, 262040206618775243
[http://dx.doi.org/10.1177/2040206618775243] [PMID: 29792071]
[51]
Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; Ray, A.S.; Cihlar, T.; Siegel, D.; Mackman, R.L.; Clarke, M.O.; Baric, R.S.; Denison, M.R. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 2018, 9(2), e00221-e18.
[http://dx.doi.org/10.1128/mBio.00221-18] [PMID: 29511076]
[52]
Saha, A.; Sharma, A.R.; Bhattacharya, M.; Sharma, G.; Lee, S-S.; Chakraborty, C. Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More. Arch. Med. Res., 2020, 51(6), 585-586.
[http://dx.doi.org/10.1016/j.arcmed.2020.05.001] [PMID: 32439198]
[53]
Tchesnokov, E.P.; Feng, J.Y.; Porter, D.P.; Götte, M. Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses, 2019, 11(4), 326.
[http://dx.doi.org/10.3390/v11040326] [PMID: 30987343]
[54]
Ko, W-C.; Rolain, J-M.; Lee, N-Y.; Chen, P-L.; Huang, C-T.; Lee, P-I.; Hsueh, P-R. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int. J. Antimicrob. Agents, 2020, 55(4)105933
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105933] [PMID: 32147516]
[55]
Amirian, E.S.; Levy, J.K. Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One Health, 2020, 9100128
[http://dx.doi.org/10.1016/j.onehlt.2020.100128] [PMID: 32258351]
[56]
Pizzorno, A.; Padey, B.; Julien, T.; Trouillet-Assant, S.; Traversier, A.; Errazuriz-Cerda, E.; Fouret, J.; Dubois, J.; Gaymard, A.; Lescure, F.X.; Dulière, V.; Brun, P.; Constant, S.; Poissy, J.; Lina, B.; Yazdanpanah, Y.; Terrier, O.; Rosa-Calatrava, M. Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia. Cell Rep Med, 2020, 1(4)100059
[http://dx.doi.org/10.1016/j.xcrm.2020.100059] [PMID: 32835306]
[57]
de Wit, E.; Feldmann, F.; Cronin, J.; Jordan, R.; Okumura, A.; Thomas, T.; Scott, D.; Cihlar, T.; Feldmann, H. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc. Natl. Acad. Sci. USA, 2020, 117(12), 6771-6776.
[http://dx.doi.org/10.1073/pnas.1922083117] [PMID: 32054787]
[58]
Williamson, B. N.; Feldmann, F.; Schwarz, B.; Meade-White, K.; Porter, D. P.; Schulz, J.; Van Doremalen, N.; Leighton, I.; Yinda, C. K.; Pérez-Pérez, L. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Preprint. BioRxiv. 2020.04.15.043166, 2020.,
[59]
GREIN, J.; OHMAGARI, N.; SHIN, D. original: Compassionate Use of Remdesivir for Patients with Severe Covid-19. N. Engl. J. Med., 382, 2327-2336.
[http://dx.doi.org/10.1056/NEJMoa2007016]
[60]
Bin, C. A Trial of Remdesivir in Adults With Mild and Moderate COVID-19., https://clinicaltrials.gov/ct2/show/NCT04252664[April 10, 2020];
[61]
UNMC. https://www.nebraskamed.com/COVID/remdesivir-speeds-up-covid-19-recovery [May 24 2020];
[62]
Zhang, L.; Zhou, R. Binding mechanism of remdesivir to SARS-CoV-2 RNA dependent RNA polymerase., 2020.
[63]
Guo, Q.; Xu, M.; Guo, S.; Zhu, F.; Xie, Y.; Shen, J. The complete synthesis of favipiravir from 2-aminopyrazine. Chem. Zvesti, 2019, 73(5), 1043-1051.
[http://dx.doi.org/10.1007/s11696-018-0654-9]
[64]
Oestereich, L.; Lüdtke, A.; Wurr, S.; Rieger, T.; Muñoz-Fontela, C.; Günther, S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res., 2014, 105, 17-21.
[http://dx.doi.org/10.1016/j.antiviral.2014.02.014] [PMID: 24583123]
[65]
Shi, F.; Li, Z.; Kong, L.; Xie, Y.; Zhang, T.; Xu, W. Synthesis and crystal structure of 6-fluoro-3-hydroxypyrazine-2-carboxamide. Drug Discov. Ther., 2014, 8(3), 117-120.
[http://dx.doi.org/10.5582/ddt.2014.01028] [PMID: 25031043]
[66]
Titova, Y.A.; Fedorova, O.V. Favipiravir–a modern antiviral drug: synthesis and modifications. Chem Heterocycl Compd (N Y), 2020, 56(6), 1-4.
[http://dx.doi.org/10.1007/s10593-020-02715-3] [PMID: 32836314]
[67]
Wang, G.; Wan, J.; Hu, Y.; Wu, X.; Prhavc, M.; Dyatkina, N.; Rajwanshi, V.K.; Smith, D.B.; Jekle, A.; Kinkade, A.; Symons, J.A.; Jin, Z.; Deval, J.; Zhang, Q.; Tam, Y.; Chanda, S.; Blatt, L.; Beigelman, L. Synthesis and anti-influenza activity of pyridine, pyridazine, and pyrimidine C-nucleosides as favipiravir (T-705) analogues. J. Med. Chem., 2016, 59(10), 4611-4624.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01933] [PMID: 27120583]
[68]
El-Nahas, A.; Hirao, K. A theoretical study on 2-hydroxypyrazine and 2, 3-dihydroxypyrazine: tautomerism, intramolecular hydrogen bond, solvent effects. J. Mol. Struct., 1999, 459(1-3), 229-237.
[http://dx.doi.org/10.1016/S0166-1280(98)00270-X]
[69]
Furuta, Y.; Takahashi, K.; Shiraki, K.; Sakamoto, K.; Smee, D.F.; Barnard, D.L.; Gowen, B.B.; Julander, J.G.; Morrey, J.D. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res., 2009, 82(3), 95-102.
[http://dx.doi.org/10.1016/j.antiviral.2009.02.198] [PMID: 19428599]
[70]
Naesens, L.; Guddat, L.W.; Keough, D.T.; van Kuilenburg, A.B.; Meijer, J.; Vande Voorde, J.; Balzarini, J. Role of human hypoxanthine guanine phosphoribosyltransferase in activation of the antiviral agent T-705 (favipiravir). Mol. Pharmacol., 2013, 84(4), 615-629.
[http://dx.doi.org/10.1124/mol.113.087247] [PMID: 23907213]
[71]
Jin, Z.; Smith, L.K.; Rajwanshi, V.K.; Kim, B.; Deval, J. The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5′-triphosphate towards influenza A virus polymerase. PLoS One, 2013, 8(7)e68347
[http://dx.doi.org/10.1371/journal.pone.0068347] [PMID: 23874596]
[72]
Chen, C.; Huang, J.; Cheng, Z.; Wu, J.; Chen, S.; Zhang, Y.; Chen, B.; Lu, M.; Luo, Y.; Zhang, J. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. MedRxiv, 2020.preprint.
[73]
Cai, Q.; Yang, M.; Liu, D.; Chen, J.; Shu, D.; Xia, J.; Liao, X.; Gu, Y.; Cai, Q.; Yang, Y. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing), 2020.,
[http://dx.doi.org/10.1016/j.eng.2020.03.007]
[74]
Huaxia. Favipiravir shows good clinical efficacy in treating COVID- 19: official., http://www.xinhuanet.com/english/2020-03/17/c_138887971.htm [September 4, 2020];
[75]
Harismah, K.; Mirzaei, M. Favipiravir: Structural Analysis and Activity against COVID-19. Adv. j. chem. Sect. B. Nat. prod. med. chem., 2020, 2(2), 55-60.,
[76]
Narkhede, R.R.; Cheke, R.S.; Ambhore, J.P.; Shinde, S.D. The molecular docking study of potential drug candidates showing anti-COVID-19 activity by exploring of therapeutic targets of SARS-CoV-2. EJMO, 2020, 4(3), 185-195.
[77]
Chung, R.T.; Gale, M., Jr; Polyak, S.J.; Lemon, S.M.; Liang, T.J.; Hoofnagle, J.H. Mechanisms of action of interferon and ribavirin in chronic hepatitis C: Summary of a workshop. Hepatology, 2008, 47(1), 306-320.
[http://dx.doi.org/10.1002/hep.22070] [PMID: 18161743]
[78]
Martin, P.; Jensen, D.M. Ribavirin in the treatment of chronic hepatitis C. J. Gastroenterol. Hepatol., 2008, 23(6), 844-855.
[http://dx.doi.org/10.1111/j.1440-1746.2008.05398.x] [PMID: 18565019]
[79]
Fernandez, H.; Banks, G.; Smith, R. Ribavirin: a clinical overview. Eur. J. Epidemiol., 1986, 2(1), 1-14.
[http://dx.doi.org/10.1007/BF00152711] [PMID: 3021519]
[80]
Rowe, T.; Banner, D.; Farooqui, A.; Ng, D.C.; Kelvin, A.A.; Rubino, S.; Huang, S.S.H.; Fang, Y.; Kelvin, D.J. In vivo ribavirin activity against severe pandemic H1N1 Influenza A/Mexico/4108/2009. J. Gen. Virol., 2010, 91(Pt 12), 2898-2906.
[http://dx.doi.org/10.1099/vir.0.024323-0] [PMID: 20797971]
[81]
Khalili, J.S.; Zhu, H.; Mak, N.S.A.; Yan, Y.; Zhu, Y. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID-19. J. Med. Virol., 2020, 92(7), 740-746.
[http://dx.doi.org/10.1002/jmv.25798] [PMID: 32227493]
[82]
Rabuffetti, M.; Bavaro, T.; Semproli, R.; Cattaneo, G.; Massone, M.; Morelli, C.F.; Speranza, G.; Ubiali, D. Synthesis of Ribavirin, Tecadenoson, and Cladribine by enzymatic transglycosylation. Catalysts, 2019, 9(4), 355.
[http://dx.doi.org/10.3390/catal9040355]
[83]
Wu, J.Z.; Larson, G.; Walker, H.; Shim, J.H.; Hong, Z. Phosphorylation of ribavirin and viramidine by adenosine kinase and cytosolic 5′-nucleotidase II: Implications for ribavirin metabolism in erythrocytes. Antimicrob. Agents Chemother., 2005, 49(6), 2164-2171.
[http://dx.doi.org/10.1128/AAC.49.6.2164-2171.2005] [PMID: 15917509]
[84]
Graci, J.D.; Cameron, C.E. Mechanisms of action of ribavirin against distinct viruses. Rev. Med. Virol., 2006, 16(1), 37-48.
[http://dx.doi.org/10.1002/rmv.483] [PMID: 16287208]
[85]
Crotty, S.; Cameron, C.; Andino, R. Ribavirin’s antiviral mechanism of action: lethal mutagenesis? J. Mol. Med. (Berl.), 2002, 80(2), 86-95.
[http://dx.doi.org/10.1007/s00109-001-0308-0] [PMID: 11907645]
[86]
Todt, D.; Walter, S.; Brown, R.J.; Steinmann, E. Mutagenic effects of ribavirin on hepatitis E virus—viral extinction versus selection of fitness-enhancing mutations. Viruses, 2016, 8(10), 283.
[http://dx.doi.org/10.3390/v8100283] [PMID: 27754363]
[87]
Bougie, I.; Bisaillon, M. The broad spectrum antiviral nucleoside ribavirin as a substrate for a viral RNA capping enzyme. J. Biol. Chem., 2004, 279(21), 22124-22130.
[http://dx.doi.org/10.1074/jbc.M400908200] [PMID: 15037606]
[88]
Katakam, P.; Adiki, S.K.; Assaleh, F.H.; Ahmed, M.M. An Update on Therapeutic Repurposing Strategies for COVID-19. Curr. Pharmacol. Rep., 2020, 6, 56-70.
[http://dx.doi.org/10.1007/s40495-020-00216-7]
[89]
Lopinavir/ Ritonavir Ribavirin and IFN-beta Combination for nCoV Treatment.,, https://clinicaltrials.gov/ct2/show/NCT04276688[February 19, 2020];
[90]
Paumgartten, F.J.R.; Delgado, I.F.; da Rocha Pitta, L.; de Oliveira, A.C.A.X. Drug repurposing clinical trials in the search for life-saving Covid-19 therapies; research targets and methodological and ethical issues. Vig Sanit Debate, 2020, 2, 39-53.
[http://dx.doi.org/10.22239/2317-269x.01596]
[91]
Elfiky, A.A. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci., 2020, 248117477
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[92]
Elfiky, A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci., 2020, 253117592
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[93]
Elfiky, A.A. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective. J. Biomol. Struct. Dyn., 2020.39(9), 3204-3212., 1-9.
[PMID: 32338164]
[94]
Patel, M.; Sheng, Y.; Mandava, N.K.; Pal, D.; Mitra, A.K. Dipeptide prodrug approach to evade efflux pumps and CYP3A4 metabolism of lopinavir. Int. J. Pharm., 2014, 476(1-2), 99-107.
[http://dx.doi.org/10.1016/j.ijpharm.2014.09.035] [PMID: 25261710]
[95]
Chandwani, A.; Shuter, J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther. Clin. Risk Manag., 2008, 4(5), 1023-1033.
[PMID: 19209283]
[96]
Adeoye, O.; Conceição, J.; Serra, P.A.; Bento da Silva, A.; Duarte, N.; Guedes, R.C.; Corvo, M.C.; Aguiar-Ricardo, A.; Jicsinszky, L.; Casimiro, T.; Cabral-Marques, H. Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method. Carbohydr. Polym., 2020, 227115287
[http://dx.doi.org/10.1016/j.carbpol.2019.115287] [PMID: 31590843]
[97]
Li, F.; Lu, J.; Ma, X. CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab. Dispos., 2012, 40(1), 18-24.
[http://dx.doi.org/10.1124/dmd.111.041400] [PMID: 21953914]
[98]
Nukoolkarn, V.; Lee, V.S.; Malaisree, M.; Aruksakulwong, O.; Hannongbua, S. Molecular dynamic simulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors. J. Theor. Biol., 2008, 254(4), 861-867.
[http://dx.doi.org/10.1016/j.jtbi.2008.07.030] [PMID: 18706430]
[99]
Ramu, E.; Rao, B.V. A short approach to the synthesis of the ritonavir and lopinavir core and its C-3 epimer via cross metathesis. Tetrahedron Asymmetry, 2009, 20(19), 2201-2204.
[http://dx.doi.org/10.1016/j.tetasy.2009.09.003]
[100]
Roy, A.; Reddy, L.A.; Dwivedi, N.; Naram, J.; Swapna, R.; Malakondaiah, G.C.; Ravikumar, M.; Bhalerao, D.; Pratap, T.B.; Reddy, P.P. Diastereoselective synthesis of a core fragment of ritonavir and lopinavir. Tetrahedron Lett., 2011, 52(51), 6968-6970.
[http://dx.doi.org/10.1016/j.tetlet.2011.10.087]
[101]
Gomes, C.R.; Moreth, M.; Cardinot, D.; Kopke, V.; Cunico, W.; da Silva Lourenço, M.C.; de Souza, M.V. Synthesis and antimycobacterial activity of novel amino alcohols containing central core of the anti-HIV drugs lopinavir and ritonavir. Chem. Biol. Drug Des., 2011, 78(6), 1031-1034.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01244.x] [PMID: 21933353]
[102]
Sham, H.L.; Betebenner, D.A.; Chen, X.; Saldivar, A.; Vasavanonda, S.; Kempf, D.J.; Plattner, J.J.; Norbeck, D.W. Synthesis and structure-activity relationships of a novel series of HIV-1 protease inhibitors encompassing ABT-378 (Lopinavir). Bioorg. Med. Chem. Lett., 2002, 12(8), 1185-1187.
[http://dx.doi.org/10.1016/S0960-894X(02)00134-8] [PMID: 11934584]
[103]
Haight, A.R.; Stuk, T.L.; Allen, M.S.; Bhagavatula, L.; Fitzgerald, M.; Hannick, S.M.; Kerdesky, F.A.; Menzia, J.A.; Parekh, S.I.; Robbins, T.A. Reduction of an enaminone: Synthesis of the diamino alcohol core of ritonavir. Org. Process Res. Dev., 1999, 3(2), 94-100.
[http://dx.doi.org/10.1021/op9802071]
[104]
Ghosh, A.K.; Bilcer, G.; Schiltz, G. Syntheses of FDA approved HIV protease inhibitors. Synthesis (Stuttg), 2001, 2001(15), 2203-2229.
[http://dx.doi.org/10.1055/s-2001-18434] [PMID: 30393404]
[105]
Stoner, E.J.; Cooper, A.J.; Dickman, D.A.; Kolaczkowski, L.; Lallaman, J.E.; Liu, J-H.; Oliver-Shaffer, P.A.; Patel, K.M.; Paterson, J.B.; Plata, D.J. Synthesis of HIV protease inhibitor ABT-378 (Lopinavir). Org. Process Res. Dev., 2000, 4(4), 264-269.
[http://dx.doi.org/10.1021/op990202j]
[106]
Anger, G.J.; Piquette-Miller, M. Mechanisms of reduced maternal and fetal lopinavir exposure in a rat model of gestational diabetes. Drug Metab. Dispos., 2011, 39(10), 1850-1859.
[http://dx.doi.org/10.1124/dmd.111.040626] [PMID: 21742899]
[107]
Kumar, G.N.; Jayanti, V.K.; Johnson, M.K.; Uchic, J.; Thomas, S.; Lee, R.D.; Grabowski, B.A.; Sham, H.L.; Kempf, D.J.; Denissen, J.F.; Marsh, K.C.; Sun, E.; Roberts, S.A. Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans. Pharm. Res., 2004, 21(9), 1622-1630.
[http://dx.doi.org/10.1023/B:PHAM.0000041457.64638.8d] [PMID: 15497688]
[108]
Sheahan, T.P.; Sims, A.C.; Leist, S.R.; Schäfer, A.; Won, J.; Brown, A.J.; Montgomery, S.A.; Hogg, A.; Babusis, D.; Clarke, M.O.; Spahn, J.E.; Bauer, L.; Sellers, S.; Porter, D.; Feng, J.Y.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun., 2020, 11(1), 222.
[http://dx.doi.org/10.1038/s41467-019-13940-6] [PMID: 31924756]
[109]
Li, G.; De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov., 2020, 19(3), 149-150.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[110]
Nutho, B.; Mahalapbutr, P.; Hengphasatporn, K.; Pattaranggoon, N.C.; Simanon, N.; Shigeta, Y.; Hannongbua, S.; Rungrotmongkol, T. Why are lopinavir and ritonavir effective against the newly emerged Coronavirus 2019? Atomistic insights into the inhibitory mechanisms. Biochemistry, 2020, 59(18), 1769-1779.
[http://dx.doi.org/10.1021/acs.biochem.0c00160] [PMID: 32293875]
[111]
Chen, F.; Chan, K.H.; Jiang, Y.; Kao, R.Y.; Lu, H.T.; Fan, K.W.; Cheng, V.C.; Tsui, W.H.; Hung, I.F.; Lee, T.S.; Guan, Y.; Peiris, J.S.; Yuen, K.Y. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J. Clin. Virol., 2004, 31(1), 69-75.
[http://dx.doi.org/10.1016/j.jcv.2004.03.003] [PMID: 15288617]
[112]
Yao, T.T.; Qian, J.D.; Zhu, W.Y.; Wang, Y.; Wang, G.Q. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J. Med. Virol., 2020, 92(6), 556-563.
[http://dx.doi.org/10.1002/jmv.25729] [PMID: 32104907]
[113]
Lim, J.; Jeon, S.; Shin, H-Y.; Kim, M.J.; Seong, Y.M.; Lee, W.J.; Choe, K-W.; Kang, Y.M.; Lee, B.; Park, S-J. Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J. Korean Med. Sci., 2020, 35(6)e79
[http://dx.doi.org/10.3346/jkms.2020.35.e79] [PMID: 32056407]
[114]
Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N. Engl. J. Med., 2020, 382(19), 1787-1799.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[115]
Schoergenhofer, C.; Jilma, B.; Stimpfl, T.; Karolyi, M.; Zoufaly, A. Pharmacokinetics of Lopinavir and Ritonavir in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19). Ann. Intern. Med., 2020, 173(8), 670-672.
[http://dx.doi.org/10.7326/M20-1550] [PMID: 32422065]
[116]
Hung, I.F-N.; Lung, K-C.; Tso, E.Y-K.; Liu, R.; Chung, T.W-H.; Chu, M-Y.; Ng, Y-Y.; Lo, J.; Chan, J.; Tam, A.R.; Shum, H.P.; Chan, V.; Wu, A.K.; Sin, K.M.; Leung, W.S.; Law, W.L.; Lung, D.C.; Sin, S.; Yeung, P.; Yip, C.C.; Zhang, R.R.; Fung, A.Y.; Yan, E.Y.; Leung, K.H.; Ip, J.D.; Chu, A.W.; Chan, W.M.; Ng, A.C.; Lee, R.; Fung, K.; Yeung, A.; Wu, T.C.; Chan, J.W.; Yan, W.W.; Chan, W.M.; Chan, J.F.; Lie, A.K.; Tsang, O.T.; Cheng, V.C.; Que, T.L.; Lau, C.S.; Chan, K.H.; To, K.K.; Yuen, K.Y. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet, 2020, 395(10238), 1695-1704.
[http://dx.doi.org/10.1016/S0140-6736(20)31042-4] [PMID: 32401715]
[117]
Osborne, V.; Davies, M.; Lane, S.; Evans, A.; Denyer, J.; Dhanda, S.; Roy, D.; Shakir, S. A. Lopinavir-Ritonavir in treatment of COVID-19: A dynamic systematic benefit-risk assessment., 2020.05(25.), 20114470..
[118]
Lin, S.; Shen, R.; Guo, X. Molecular modeling evaluation of the binding abilities of ritonavir and lopinavir to Wuhan pneumonia coronavirus proteases. bioRxiv, 2020.
[119]
Muralidharan, N.; Sakthivel, R.; Velmurugan, D.; Gromiha, M.M. Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 protease against COVID-19. J. Biomol. Struct. Dyn., 2020, 1-6.
[http://dx.doi.org/10.1080/07391102.2020.1752802] [PMID: 32248766]
[120]
Ghosh, A.K. Capturing the essence of organic synthesis: from bioactive natural products to designed molecules in today’s medicine. J. Org. Chem., 2010, 75(23), 7967-7989.
[http://dx.doi.org/10.1021/jo101606g] [PMID: 20936876]
[121]
Dierynck, I.; Van Marck, H.; Van Ginderen, M.; Jonckers, T.H.; Nalam, M.N.; Schiffer, C.A.; Raoof, A.; Kraus, G.; Picchio, G. TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. Antimicrob. Agents Chemother., 2011, 55(12), 5723-5731.
[http://dx.doi.org/10.1128/AAC.00748-11] [PMID: 21896904]
[122]
Harrison, C. Coronavirus puts drug repurposing on the fast track. Nat. Biotechnol., 2020, 38(4), 379-381.
[http://dx.doi.org/10.1038/d41587-020-00003-1] [PMID: 32205870]
[123]
Catapang, J. K.; Billones, J. B. On the generation of novel ligands for SARS-CoV-2 protease and ACE2 receptor via constrained graph variational autoencoders., [March 24, 2020];
[http://dx.doi.org/10.26434/chemrxiv.12011157.v3]
[124]
Mathias, A.A.; German, P.; Murray, B.P.; Wei, L.; Jain, A.; West, S.; Warren, D.; Hui, J.; Kearney, B.P. Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin. Pharmacol. Ther., 2010, 87(3), 322-329.
[http://dx.doi.org/10.1038/clpt.2009.228] [PMID: 20043009]
[125]
Balayan, T.; Horvath, H.; Rutherford, G.W. Ritonavir-boosted darunavir plus two nucleoside reverse transcriptase inhibitors versus other regimens for initial antiretroviral therapy for people with HIV infection: a systematic review. AIDS Res. Ther., 2017.
[http://dx.doi.org/10.1155/2017/2345617]
[126]
Ruela Corrêa, J.C.; D’Arcy, D.M.; dos Reis Serra, C.H.; Nunes Salgado, H.R. Darunavir: a critical review of its properties, use and drug interactions. Pharmacology, 2012, 90(1-2), 102-109.
[http://dx.doi.org/10.1159/000339862] [PMID: 22797653]
[127]
Rapolu, R.K.; Areveli, S.; Raju, V.P.; Navuluri, S.; Chavali, M.; Mulakayala, N. An Efficient Synthesis of Darunavir Substantially Free from Impurities: Synthesis and Characterization of Novel Impurities. ChemistrySelect, 2019, 4(14), 4422-4427.
[http://dx.doi.org/10.1002/slct.201803825]
[128]
Surleraux, D.L.; de Kock, H.A.; Verschueren, W.G.; Pille, G.M.; Maes, L.J.; Peeters, A.; Vendeville, S.; De Meyer, S.; Azijn, H.; Pauwels, R.; de Bethune, M.P.; King, N.M.; Prabu-Jeyabalan, M.; Schiffer, C.A.; Wigerinck, P.B. Design of HIV-1 protease inhibitors active on multidrug-resistant virus. J. Med. Chem., 2005, 48(6), 1965-1973.
[http://dx.doi.org/10.1021/jm049454n] [PMID: 15771440]
[129]
Vermeir, M.; Lachau-Durand, S.; Mannens, G.; Cuyckens, F.; van Hoof, B.; Raoof, A. Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects. Drug Metab. Dispos., 2009, 37(4), 809-820.
[http://dx.doi.org/10.1124/dmd.108.024109] [PMID: 19131522]
[130]
Chen, J.; Xia, L.; Liu, L.; Xu, Q.; Ling, Y.; Huang, D.; Huang, W.; Song, S.; Xu, S.; Shen, Y. Antiviral Activity and Safety of DarunaThe Situation of Small Molecules Targeting Key Proteins Mini-Reviews in Medicinal Chemistry, 2022, Vol. 22, No. 2 309 vir/Cobicistat for Treatment of COVID-19Open Forum Infectious Diseases; Laura, A. N.; Malgorzata, M.; Alessio, S.; Antonio, D. B.; Federica, P.; Antonio, V.; Mauro, G.; Matteo, B., Eds.; Oxford University Press: US, 2020. 21June;.
[131]
Costanzo, M.; De Giglio, M.A.R.; Roviello, G.N. SARS-CoV-2: recent reports on antiviral therapies based on lopinavir/ritonavir, darunavir/umifenovir, hydroxychloroquine, remdesivir, favipiravir and other drugs for the treatment of the new coronavirus. Curr. Med. Chem., 2020, 27(27), 4536-4541.
[http://dx.doi.org/10.2174/0929867327666200416131117] [PMID: 32297571]
[132]
Riva, A.; Conti, F.; Bernacchia, D.; Pezzati, L.; Sollima, S.; Merli, S.; Siano, M.; Lupo, A.; Rusconi, S.; Cattaneo, D.; Gervasoni, C. Darunavir does not prevent SARS-CoV-2 infection in HIV patients. Pharmacol. Res., 2020, 157104826
[http://dx.doi.org/10.1016/j.phrs.2020.104826] [PMID: 32325127]
[133]
Ning, Q.; Han, M.A. Randomized, Open, Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia., 2019. https://clinicaltrials.gov/ct2/show/NCT04261270[March 17, 2020];
[134]
Lin, S.; Shen, R.; He, J.; Li, X.; Guo, X. Molecular modeling evaluation of the binding effect of ritonavir, lopinavir and darunavir to severe acute respiratory syndrome coronavirus 2 proteases. bioRxiv, 2020.
[135]
Devaux, C.A.; Rolain, J-M.; Colson, P.; Raoult, D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int. J. Antimicrob. Agents, 2020, 55(5)105938
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[136]
Inglot, A.D. Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs. J. Gen. Virol., 1969, 4(2), 203-214.
[http://dx.doi.org/10.1099/0022-1317-4-2-203] [PMID: 4306296]
[137]
Miller, D.K.; Lenard, J. Antihistaminics, local anesthetics, and other amines as antiviral agents. Proc. Natl. Acad. Sci. USA, 1981, 78(6), 3605-3609.
[http://dx.doi.org/10.1073/pnas.78.6.3605] [PMID: 6115382]
[138]
Mizui, T.; Yamashina, S.; Tanida, I.; Takei, Y.; Ueno, T.; Sakamoto, N.; Ikejima, K.; Kitamura, T.; Enomoto, N.; Sakai, T.; Kominami, E.; Watanabe, S. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J. Gastroenterol., 2010, 45(2), 195-203.
[http://dx.doi.org/10.1007/s00535-009-0132-9] [PMID: 19760134]
[139]
Ooi, E.E.; Chew, J.S.W.; Loh, J.P.; Chua, R.C. In vitro inhibition of human influenza A virus replication by chloroquine. Virol. J., 2006, 3(1), 39.
[http://dx.doi.org/10.1186/1743-422X-3-39] [PMID: 16729896]
[140]
de Wilde, A.H.; Jochmans, D.; Posthuma, C.C.; Zevenhoven-Dobbe, J.C.; van Nieuwkoop, S.; Bestebroer, T.M.; van den Hoogen, B.G.; Neyts, J.; Snijder, E.J. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob. Agents Chemother., 2014, 58(8), 4875-4884.
[http://dx.doi.org/10.1128/AAC.03011-14] [PMID: 24841269]
[141]
Dowall, S.D.; Bosworth, A.; Watson, R.; Bewley, K.; Taylor, I.; Rayner, E.; Hunter, L.; Pearson, G.; Easterbrook, L.; Pitman, J.; Hewson, R.; Carroll, M.W. Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model. J. Gen. Virol., 2015, 96(12), 3484-3492.
[http://dx.doi.org/10.1099/jgv.0.000309] [PMID: 26459826]
[142]
Keyaerts, E.; Li, S.; Vijgen, L.; Rysman, E.; Verbeeck, J.; Van Ranst, M.; Maes, P. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob. Agents Chemother., 2009, 53(8), 3416-3421.
[http://dx.doi.org/10.1128/AAC.01509-08] [PMID: 19506054]
[143]
Sahraei, Z.; Shabani, M.; Shokouhi, S.; Saffaei, A. Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine. Int. J. Antimicrob. Agents, 2020, 105945(10.1016).
[144]
Shen, L.; Yang, Y.; Ye, F.; Liu, G.; Desforges, M.; Talbot, P.J.; Tan, W. Safe and sensitive antiviral screening platform based on recombinant human coronavirus OC43 expressing the luciferase reporter gene. Antimicrob. Agents Chemother., 2016, 60(9), 5492-5503.
[http://dx.doi.org/10.1128/AAC.00814-16] [PMID: 27381385]
[145]
Jeon, K.W. International review of cytology; Academic Press, 1996.
[146]
Al-Bari, M.A.A. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J. Antimicrob. Chemother., 2015, 70(6), 1608-1621.
[http://dx.doi.org/10.1093/jac/dkv018] [PMID: 25693996]
[147]
BACHMAN, G. B.; Bennett, G. E.; Barker, R. S. Synthesis of substituted quinolylamines. Derivatives of 4-amino-7-chloroquinoline. J. Org. Chem., 1950, 15(6), 1278-1284.
[http://dx.doi.org/10.1021/jo01152a025]
[148]
Parnham, M.J. Compendium of inflammatory diseases, 1st ed; Springer Basel: USA, 2016.
[http://dx.doi.org/10.1007/978-3-7643-8550-7]
[149]
Smit, C.; Peeters, M.Y.M.; van den Anker, J.N.; Knibbe, C.A.J. Chloroquine for SARS-CoV-2: Implications of its unique pharmacokinetic and safety properties. Clin. Pharmacokinet., 2020, 59(6), 659-669.
[http://dx.doi.org/10.1007/s40262-020-00891-1] [PMID: 32306288]
[150]
Wu, C.; Liu, Y.; Yang, Y.; Zhang, P.; Zhong, W.; Wang, Y.; Wang, Q.; Xu, Y.; Li, M.; Li, X.; Zheng, M.; Chen, L.; Li, H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B, 2020, 10(5), 766-788.
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[151]
Cortegiani, A.; Ingoglia, G.; Ippolito, M.; Giarratano, A.; Einav, S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J. Crit. Care, 2020, 57, 279-283.
[http://dx.doi.org/10.1016/j.jcrc.2020.03.005] [PMID: 32173110]
[152]
Gautret, P.; Lagier, J-C.; Parola, P.; Hoang, V.T.; Meddeb, L.; Mailhe, M.; Doudier, B.; Courjon, J.; Giordanengo, V.; Vieira, V.E.; Tissot Dupont, H.; Honoré, S.; Colson, P.; Chabrière, E.; La Scola, B.; Rolain, J.M.; Brouqui, P.; Raoult, D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents, 2020, 56(1)105949
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[153]
Gautret, P.; Lagier, J-C.; Parola, P.; Hoang, V.T.; Meddeb, L.; Sevestre, J.; Mailhe, M.; Doudier, B.; Aubry, C.; Amrane, S.; Seng, P.; Hocquart, M.; Eldin, C.; Finance, J.; Vieira, V.E.; Tissot-Dupont, H.T.; Honoré, S.; Stein, A.; Million, M.; Colson, P.; La Scola, B.; Veit, V.; Jacquier, A.; Deharo, J.C.; Drancourt, M.; Fournier, P.E.; Rolain, J.M.; Brouqui, P.; Raoult, D. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med. Infect. Dis., 2020, 34101663
[http://dx.doi.org/10.1016/j.tmaid.2020.101663] [PMID: 32289548]
[154]
Huang, M.; Tang, T.; Pang, P.; Li, M.; Ma, R.; Lu, J.; Shu, J.; You, Y.; Chen, B.; Liang, J.; Hong, Z.; Chen, H.; Kong, L.; Qin, D.; Pei, D.; Xia, J.; Jiang, S.; Shan, H. Treating COVID-19 with Chloroquine. J. Mol. Cell Biol., 2020, 12(4), 322-325.
[http://dx.doi.org/10.1093/jmcb/mjaa014] [PMID: 32236562]
[155]
Savarino, A. Use of chloroquine in viral diseases. Lancet Infect. Dis., 2011, 11(9), 653-654.
[http://dx.doi.org/10.1016/S1473-3099(11)70092-5] [PMID: 21550312]
[156]
Jankelson, L.; Karam, G.; Becker, M.L.; Chinitz, L.A.; Tsai, M-C. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm, 2020, 17(9), 1472-1479.
[http://dx.doi.org/10.1016/j.hrthm.2020.05.008] [PMID: 32438018]
[157]
Omar, S.; Bouziane, I.; Bouslama, Z.; Djemel, A. In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2.,. 2020.
[158]
Barik, A.; Rai, G.; Modi, G. .Molecular docking and binding mode analysis of selected FDA approved drugs against COVID-19 selected key protein targets: An effort towards drug repurposing to identify the combination therapy to combat COVID-19. arXiv preprint arXiv:2004.06447, 2020..
[159]
Bouchentouf, S.; Missoum, N. Identification of Compounds from Nigella Sativa as New Potential Inhibitors of, 2019. [March 31, 2020];.
[http://dx.doi.org/10.26434/chemrxiv.12055716.v1]
[160]
Peele, K.A.; Potla Durthi, C.; Srihansa, T.; Krupanidhi, S.; Ayyagari, V.S.; Babu, D.J.; Indira, M.; Reddy, A.R.; Venkateswarulu, T.C. Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study. Inform Med Unlocked, 2020, 19100345
[http://dx.doi.org/10.1016/j.imu.2020.100345] [PMID: 32395606]
[161]
Srivastava, A.K.; Kumar, A.; Tiwari, G.; Kumar, R.; Misra, N. Silico Investigations on the Potential Inhibitors for COVID-19 Protease. arXiv:2003.10642,, 2020.
[162]
Beura, S.; Prabhakar, C. In-silico strategies for probing chloroquine based inhibitors against SARS-CoV-2. Journal of Biomolecular Structure and Dynamics, 2020, (just-accepted), 1-25.
[http://dx.doi.org/10.1080/07391102.2020.1772111]
[163]
Fantini, J.; Di Scala, C.; Chahinian, H.; Yahi, N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int. J. Antimicrob. Agents, 2020, 55(5)105960
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105960] [PMID: 32251731]
[164]
Huang, L.; Zhang, L.; Liu, Y.; Luo, R.; Zeng, L.; Telegina, I.; Vlassov, V.V. Arbidol for preventing and treating influenza in adults and children. Cochrane Database Syst. Rev., 2017, 2.
[http://dx.doi.org/10.1002/14651858.CD011489.pub2]
[165]
Trofimov, F.; Tsyshkova, N.; Zotova, S.; Grinev, A. Synthesis of a new antiviral agent, arbidole. Pharm. Chem. J., 1993, 27(1), 75-76.
[http://dx.doi.org/10.1007/BF00772858]
[166]
Blaising, J.; Polyak, S.J.; Pécheur, E-I. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res., 2014, 107, 84-94.
[http://dx.doi.org/10.1016/j.antiviral.2014.04.006] [PMID: 24769245]
[167]
Pécheur, E-I.; Lavillette, D.; Alcaras, F.; Molle, J.; Boriskin, Y.S.; Roberts, M.; Cosset, F-L.; Polyak, S.J. Biochemical mechanism of hepatitis C virus inhibition by the broad-spectrum antiviral arbidol. Biochemistry, 2007, 46(20), 6050-6059.
[http://dx.doi.org/10.1021/bi700181j] [PMID: 17455911]
[168]
Sellitto, G. Design and synthesis of “small molecules” as antiviral and radiotracer agents.,, 2011.
[169]
Amanat, F.; Krammer, F. SARS-CoV-2 vaccines: status report. Immunity, 2020, 52(4), 583-589.
[http://dx.doi.org/10.1016/j.immuni.2020.03.007] [PMID: 32259480]
[170]
Teissier, E.; Zandomeneghi, G.; Loquet, A.; Lavillette, D.; Lavergne, J-P.; Montserret, R.; Cosset, F-L.; Böckmann, A.; Meier, B.H.; Penin, F.; Pécheur, E.I. Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol. PLoS One, 2011, 6(1)e15874
[http://dx.doi.org/10.1371/journal.pone.0015874] [PMID: 21283579]
[171]
Eren, E.; Saribek, F.; Kalayci, Z.; Yilmaz, N. How to cripple SARS-COV-2 virus with Ozone treatment., 2020.2, 1094-1102..
[172]
Deng, L.; Li, C.; Zeng, Q.; Liu, X.; Li, X.; Zhang, H.; Hong, Z.; Xia, J. Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study. J. Infect., 2020, 81(1), e1-e5.
[http://dx.doi.org/10.1016/j.jinf.2020.03.002] [PMID: 32171872]
[173]
Xu, K.; Chen, Y.; Yuan, J.; Yi, P.; Ding, C.; Wu, W.; Li, Y.; Ni, Q.; Zhou, R.; Li, X. Clinical Efficacy of Arbidol in Patients with 2019 Novel Coronavirus-Infected Pneumonia: A Retrospective Cohort Study; SSRN, 2020.
[174]
Rosa, S.G.V.; Santos, W.C. Clinical trials on drug repositioning for COVID-19 treatment. Rev. Panam. Salud Publica, 2020, 44e40
[http://dx.doi.org/10.26633/RPSP.2020.40] [PMID: 32256547]
[175]
Huynh, T.; Luan, B. in silico Exploration of Molecular Mechanism and Potency Ranking of Clinically Oriented Drugs for Inhibiting SARS-CoV-2’s Main Protease. J. Phys. Chem. Lett., 2020, 11, 4413-4420.
[http://dx.doi.org/10.1021/acs.jpclett.0c00994] [PMID: 32406687]
[176]
Fujii, S.; Hitomi, Y. New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim. Biophys. Acta, 1981, 661(2), 342-345.
[http://dx.doi.org/10.1016/0005-2744(81)90023-1] [PMID: 6271224]
[177]
Chen, X.; Xu, Z.; Zeng, S.; Wang, X.; Liu, W.; Qian, L.; Wei, J.; Yang, X.; Shen, Q.; Gong, Z.; Yan, Y. The molecular aspect of antitumor effects of protease inhibitor nafamostat mesylate and its role in potential clinical applications. Front. Oncol., 2019, 9, 852.
[http://dx.doi.org/10.3389/fonc.2019.00852] [PMID: 31552177]
[178]
Gibo, J.; Ito, T.; Kawabe, K.; Hisano, T.; Inoue, M.; Fujimori, N.; Oono, T.; Arita, Y.; Nawata, H. Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity. Lab. Invest., 2005, 85(1), 75-89.
[http://dx.doi.org/10.1038/labinvest.3700203] [PMID: 15531908]
[179]
Hosoya, M.; Matsuyama, S.; Baba, M.; Suzuki, H.; Shigeta, S. Effects of protease inhibitors on replication of various myxoviruses. Antimicrob. Agents Chemother., 1992, 36(7), 1432-1436.
[http://dx.doi.org/10.1128/AAC.36.7.1432] [PMID: 1510439]
[180]
Someya, A.; Tanaka, N.; Okuyama, A. Inhibition of influenza virus A/WSN replication by a trypsin inhibitor, 6-amidino-2-naphthyl p-guanidinobenzoate. Biochem. Biophys. Res. Commun., 1990, 169(1), 148-152.
[http://dx.doi.org/10.1016/0006-291X(90)91446-Y] [PMID: 2350338]
[181]
Nishimura, H.; Yamaya, M. A synthetic serine protease inhibitor, Nafamostat Mesilate, is a drug potentially applicable to the treatment of ebola virus disease. Tohoku J. Exp. Med., 2015, 237(1), 45-50.
[http://dx.doi.org/10.1620/tjem.237.45] [PMID: 26346967]
[182]
Chen, B.; LI, C.; SHI, Y. Synthetic process for camostat mesilate. A drug for pancreatitis treatment Huagong Jinzhan, 2010, 29(7), 1334-1337..
[183]
Okajima, K.; Uchiba, M.; Murakami, K. Nafamostat mesilate. Cardiovasc. Drug Rev., 1995, 13(1), 51-65.
[http://dx.doi.org/10.1111/j.1527-3466.1995.tb00213.x]
[184]
Yamaori, S.; Fujiyama, N.; Kushihara, M.; Funahashi, T.; Kimura, T.; Yamamoto, I.; Sone, T.; Isobe, M.; Ohshima, T.; Matsumura, K.; Oda, M.; Watanabe, K. Involvement of human blood arylesterases and liver microsomal carboxylesterases in nafamostat hydrolysis. Drug Metab. Pharmacokinet., 2006, 21(2), 147-155.
[http://dx.doi.org/10.2133/dmpk.21.147] [PMID: 16702735]
[185]
Midgley, I.; Hood, A.J.; Proctor, P.; Chasseaud, L.F.; Irons, S.R.; Cheng, K.N.; Brindley, C.J.; Bonn, R. Metabolic fate of 14C-camostat mesylate in man, rat and dog after intravenous administration. Xenobiotica, 1994, 24(1), 79-92.
[http://dx.doi.org/10.3109/00498259409043223] [PMID: 8165824]
[186]
Hedstrom, L. Serine protease mechanism and specificity. Chem. Rev., 2002, 102(12), 4501-4524.
[http://dx.doi.org/10.1021/cr000033x] [PMID: 12475199]
[187]
Paoloni-Giacobino, A.; Chen, H.; Peitsch, M.C.; Rossier, C.; Antonarakis, S.E. Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. Genomics, 1997, 44(3), 309-320.
[http://dx.doi.org/10.1006/geno.1997.4845] [PMID: 9325052]
[188]
Heurich, A.; Hofmann-Winkler, H.; Gierer, S.; Liepold, T.; Jahn, O.; Pöhlmann, S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the SARS-coronavirus spike-protein. J. Virol., 2013, 88(2), 1293-1307.
[http://dx.doi.org/10.1128/JVI.02202-13] [PMID: 24227843]
[189]
Meyer, D.; Sielaff, F.; Hammami, M.; Böttcher-Friebertshäuser, E.; Garten, W.; Steinmetzer, T. Identification of the first synthetic inhibitors of the type II transmembrane serine protease TMPRSS2 suitable for inhibition of influenza virus activation. Biochem. J., 2013, 452(2), 331-343.
[http://dx.doi.org/10.1042/BJ20130101] [PMID: 23527573]
[190]
Sonawane, K.; Barale, S. S.; Dhanavade, M. J.; Waghmare, S. R.; Nadaf, N. H.; Kamble, S. A.; Mohammed, A. A.; Makandar, A. M.; Fandilolu, P. M.; Dound, A. S. Homology Modeling and Docking Studies of TMPRSS2 with Experimentally Known Inhibitors Camostat Mesylate, Nafamostat and Bromhexine Hydrochloride to Control SARS-Coronavirus-2.. 2020.
[191]
Yamamoto, M.; Matsuyama, S.; Li, X.; Takeda, M.; Kawaguchi, Y.; Inoue, J.I.; Matsuda, Z. Identification of nafamostat as a potent inhibitor of Middle East respiratory syndrome coronavirus S protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob. Agents Chemother., 2016, 60(11), 6532-6539.
[http://dx.doi.org/10.1128/AAC.01043-16] [PMID: 27550352]
[192]
Inoue, J.; Yamamoto, M. Identification of an existing Japanese pancreatitis drug, Nafamostat, which is expected to prevent the transmission of new coronavirus infection (COVID-19); Tokyo; , 2020.
[193]
Tang, N.; Li, D.; Wang, X.; Sun, Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost., 2020, 18(4), 844-847.
[http://dx.doi.org/10.1111/jth.14768] [PMID: 32073213]
[194]
Kumar, R.; Harilal, S.; Al-Sehemi, A.G.; Mathew, G.E.; Carradori, S.; Mathew, B. The Chronicle of COVID-19 and Possible Strategies to Curb the Pandemic. Curr. Med. Chem., 2020.
[http://dx.doi.org/10.2174/0929867327666200702151018] [PMID: 32614740]
[195]
Farina, N.; Ramirez, G.A.; De Lorenzo, R.; Di Filippo, L.; Conte, C.; Ciceri, F.; Manfredi, A.A.; Rovere-Querini, P. COVID-19: Pharmacology and kinetics of viral clearance. Pharmacol. Res., 2020, 161105114
[http://dx.doi.org/10.1016/j.phrs.2020.105114] [PMID: 32758635]
[196]
Frediansyah, A.; Nainu, F.; Dhama, K.; Mudatsir, M.; Harapan, H. Remdesivir and its antiviral activity against COVID-19: A systematic review. Clin. Epidemiol. Glob. Health, 2020.
[PMID: 32838064]
[197]
Singh, A.K.; Singh, A.; Singh, R.; Misra, A. Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies. Diabetes Metab. Syndr., 2020, 14(4), 641-648.
[http://dx.doi.org/10.1016/j.dsx.2020.05.018] [PMID: 32428865]
[198]
Agrawal, U.; Raju, R.; Udwadia, Z.F. Favipiravir: A new and emerging antiviral option in COVID-19. Med. J. Armed Forces India, 2020, 76(4), 370-376.
[http://dx.doi.org/10.1016/j.mjafi.2020.08.004] [PMID: 32895599]
[199]
Joshi, S.; Parkar, J.; Ansari, A.; Vora, A.; Talwar, D.; Tiwaskar, M.; Patil, S.; Barkate, H. Role of favipiravir in the treatment of COVID-19. Int. J. Infect. Dis., 2020.
[http://dx.doi.org/10.1016/j.ijid.2020.10.069] [PMID: 33130203]
[200]
Pilkington, V.; Pepperrell, T.; Hill, A. A review of the safety of favipiravir - a potential treatment in the COVID-19 pandemic? J. Virus Erad., 2020, 6(2), 45-51.
[http://dx.doi.org/10.1016/S2055-6640(20)30016-9] [PMID: 32405421]
[201]
Tong, S.; Su, Y.; Yu, Y.; Wu, C.; Chen, J.; Wang, S.; Jiang, J. Ribavirin therapy for severe COVID-19: a retrospective cohort study. Int. J. Antimicrob. Agents, 2020, 56(3)106114
[http://dx.doi.org/10.1016/j.ijantimicag.2020.106114] [PMID: 32712334]
[202]
Magro, P.; Zanella, I.; Pescarolo, M.; Castelli, F.; Quiros-Roldan, E. Lopinavir/ritonavir: repurposing an old drug for HIV infection in COVID-19 treatment. Biomed. J., 2020.
[http://dx.doi.org/10.1016/j.bj.2020.11.005]
[203]
Jomah, S.; Asdaq, S.M.B.; Al-Yamani, M.J. Clinical efficacy of antivirals against novel coronavirus (COVID-19): A review. J. Infect. Public Health, 2020, 13(9), 1187-1195.
[http://dx.doi.org/10.1016/j.jiph.2020.07.013] [PMID: 32773212]
[204]
Rodrigo, C.; Fernando, S.D.; Rajapakse, S. Clinical evidence for repurposing chloroquine and hydroxychloroquine as antiviral agents: a systematic review. Clin. Microbiol. Infect., 2020, 26(8), 979-987.
[http://dx.doi.org/10.1016/j.cmi.2020.05.016] [PMID: 32470568]
[205]
Alves, V.M.; Bobrowski, T.; Melo‐Filho, C.C.; Korn, D.; Auerbach, S.; Schmitt, C.; Muratov, E.N.; Tropsha, A. QSAR Modeling of SARS‐CoV Mpro Inhibitors Identifies Sufugolix, Cenicriviroc, Proglumetacin, and Other Drugs as Candidates for Repurposing against SARS-CoV-2. Mol. Inform., 2020.
[PMID: 33405340]
[206]
Ivanov, J.; Polshakov, D.; Kato-Weinstein, J.; Zhou, Q.; Li, Y.; Granet, R.; Garner, L.; Deng, Y.; Liu, C.; Albaiu, D.; Wilson, J.; Aultman, C. Quantitative Structure-Activity Relationship Machine Learning Models and their Applications for Identifying Viral 3CLpro- and RdRp-Targeting Compounds as Potential Therapeutics for COVID-19 and Related Viral Infections. ACS Omega, 2020, 5(42), 27344-27358.
[http://dx.doi.org/10.1021/acsomega.0c03682] [PMID: 33134697]
[207]
Mahapatra, S.; Nath, P.; Chatterjee, M.; Das, N.; Kalita, D.; Roy, P.; Satapathi, S. . Repurposing Therapeutics for COVID-19: Rapid Prediction of Commercially available drugs through Machine Learning and Docking. medRxiv, , 2020.
[208]
Sheahan, T. P.; Sims, A. C.; Zhou, S.; Hill, C.; Leist, S. R.; Schaefer, A.; Agostini, M.; Pruijssers, A.; Brown, A. J.; Bluemling, G. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus., 2020.03.(19.), 997890; [March 20, 2020];.
[http://dx.doi.org/10.1101/2020.03.19.99789 ]
[209]
Sheahan, T.P.; Sims, A.C.; Zhou, S.; Graham, R.L.; Pruijssers, A.J.; Agostini, M.L.; Leist, S.R.; Schäfer, A.; Dinnon, K.H., III; Stevens, L.J.; Chappell, J.D.; Lu, X.; Hughes, T.M.; George, A.S.; Hill, C.S.; Montgomery, S.A.; Brown, A.J.; Bluemling, G.R.; Natchus, M.G.; Saindane, M.; Kolykhalov, A.A.; Painter, G.; Harcourt, J.; Tamin, A.; Thornburg, N.J.; Swanstrom, R.; Denison, M.R.; Baric, R.S. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med., 2020, 12(541)eabb5883
[http://dx.doi.org/10.1126/scitranslmed.abb5883] [PMID: 32253226]
[210]
Kouznetsov, V.V. COVID-19 treatment: Much research and testing, but far, few magic bullets against SARS-CoV-2 coronavirus. Eur. J. Med. Chem., 2020, 203112647
[http://dx.doi.org/10.1016/j.ejmech.2020.112647] [PMID: 32693298]
[211]
Toots, M.; Yoon, J-J.; Hart, M.; Natchus, M.G.; Painter, G.R.; Plemper, R.K. Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model. Transl. Res., 2020, 218, 16-28.
[http://dx.doi.org/10.1016/j.trsl.2019.12.002] [PMID: 31945316]
[212]
Abuo-Rahma, G.E-D.A.; Mohamed, M.F.; Ibrahim, T.S.; Shoman, M.E.; Samir, E.; Abd El-Baky, R.M. Potential repurposed SARS-CoV-2 (COVID-19) infection drugs. RSC Advances, 2020, 10(45), 26895-26916.
[http://dx.doi.org/10.1039/D0RA05821A]
[213]
Zumla, A.; Chan, J.F.; Azhar, E.I.; Hui, D.S.; Yuen, K-Y. Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov., 2016, 15(5), 327-347.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[214]
Francini, E.; Miano, S.T.; Fiaschi, A.I.; Francini, G. Doxycycline or minocycline may be a viable treatment option against SARS-CoV-2. Med. Hypotheses, 2020, 144110054
[http://dx.doi.org/10.1016/j.mehy.2020.110054] [PMID: 32758890]
[215]
Maurya, D. K. A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients., [Jul 9, 2020];.
[http://dx.doi.org/10.26434/chemrxiv.12630539.v1]
[216]
Caly, L.; Druce, J.D.; Catton, M.G.; Jans, D.A.; Wagstaff, K.M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res., 2020, 178104787
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[217]
Heidary, F.; Gharebaghi, R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J. Antibiot. (Tokyo), 2020, 73(9), 593-602.
[http://dx.doi.org/10.1038/s41429-020-0336-z] [PMID: 32533071]
[218]
SEHAILIA M..
[219]
Burkard, C.; Verheije, M.H.; Haagmans, B.L.; van Kuppeveld, F.J.; Rottier, P.J.; Bosch, B-J.; de Haan, C.A. ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells. J. Virol., 2015, 89(8), 4434-4448.
[http://dx.doi.org/10.1128/JVI.03274-14] [PMID: 25653449]
[220]
Cho, J.; Lee, Y.J.; Kim, J-H.; Kim, S.I.; Kim, S.S.; Choi, B-S.; Choi, J-H. Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19. Sci. Rep., 2020, 10(1), 16200.
[http://dx.doi.org/10.1038/s41598-020-72879-7] [PMID: 33004837]
[221]
Farag, A.; Wang, P.; Boys, I. N.; Eitson, J. L.; Ohlson, M. B.; Fan, W.; McDougal, M. B.; Ahmed, M.; Schoggins, J. W.; Sadek, H. Identification of Atovaquone, Ouabain and Mebendazole as FDA Approved Drugs Tar-geting SARS-CoV-2 (Version 4). Research square, 2020..
[http://dx.doi.org/10.21203/rs.21203.rs-34731/v21201.]

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